This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Two groups of macaques were infected with a lethal dose of high-virulence Mtb Erdman strain. 17 weeks prior to this, one group had been vaccinated with BCG while another group had been sham-vaccinated. Our results indicate that BCG significantly and effectively protected NHPs against challenge with a lethal-dose of Mtb. Relative to sham-vaccinated animals, the BCG-vaccinated animals survived, exhibited fewer lung lesions and Mtb load, and lower expression of inflammatory markers. These animals also exhibited a more robust CD8-specific immune response in the lungs of NHPs. In sham-vaccinated animals, we observed a transcriptional reprogramming between 1 and 2 months after infection, similar to that reported by us for rhesus macaques infected with high-dose Mtb via aerosol. Gene-expression and cellular recruitment differences between these two groups of NHPs will allow us to generate a robust multi-factorial expression set that can be used as future biomarkers of progression of and protection from TB infections in humans.